Common Name(s): 5-HTP , 5-hydroxytryptophan . Extracts of Griffonia simplicifolia are found in commercial preparations such as Relarian and MiniChill .

Uses

Clinical trials of 5-HTP conducted in various conditions have resulted in limited evidence suggesting a place in therapy for anxiety, depression, and neurological conditions in which a serotonin deficiency is a contributory factor. 5-HTP may also be an effective appetite suppressant, but further clinical trials are needed.

Dosing

Recent clinical trials do not provide adequate dosing guidelines. Studies in depression have used 5-HTP 200 to 300 mg/day given in 3 to 4 divided doses to prevent possible nausea.

Contraindications

The potential for serotonin syndrome exists with concomitant use of selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs).

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

The potential for serotonin syndrome exists with concomitant use of SSRIs or MAOIs. 5-HTP augments the effect of citalopram and clomipramine, while carbidopa increases the bioavailability of 5-HTP.

Adverse Reactions

Nausea and vomiting are the most common dose-related adverse events. Diarrhea, abdominal pain, mild headache, and sleepiness have also been reported.

Toxicology

There is little information on the toxicology of 5-HTP. A possible association with fatal eosinophilia-myalgia syndrome in the 1980s and 1990s has now been attributed to contaminated L-tryptophan.

Botany

Seeds from the woody climbing shrub G. simplicifolia are used as a source of 5-HTP. The plant can grow to 3 m and is found in tropical Africa, most prevalently in Ghana. It has brown-black branches with simple, large, alternate leaves. The flowers are tubular pale green/orange, and the fruit is an oblique cylindrical black pod, approximately 8 cm long and 4 cm wide, containing the seeds.

History

The whole plant is used in African traditional medicine. The pulped bark is used topically on syphilitic sores, and a paste made from the leaves is applied to burns. The leaf sap is used for inflamed eyes, while decoctions made from the stem and leaves are used as a purgative, to relieve constipation, and as a topical antiseptic.

Chewing the stems is said to provide an aphrodisiac effect, and the leaves are regarded as a good food source for animals. The plant is an industrial source of 5-HTP, with Ghana exporting raw materials mostly to Germany.

Chemistry

The leaves of the plant have a high protein content and contain phosphorus and calcium, as well as a volatile oil, coumarins, and 5-HTP and 5-hydroxytryptamine. The ripe seeds contain as much as 20% 5-HTP and lectins of interest in cancer and neurological research. High-performance liquid chromatography (HPLC) assay methods have been described for the quantification of 5-HTP. ,

Uses and Pharmacology

Tryptophan, an essential amino acid, is obtained from animal protein in a Western diet. It is enzymatically converted to 5-HTP by tryptophan hydroxylase, which is further converted to serotonin. Factors that may influence the rate-limiting hydroxylase step in 5-HTP production include stress, insulin resistance, vitamin B 6 deficiency, and insufficient magnesium. , Depleted states of serotonin have been implicated in neurological disorders such as autism, epilepsy, depression, and migraine, among other conditions. , , , ,

5-HTP is used by some researchers as a challenge test to examine central serotonergic function, with cortisol and prolactin release used as a measure of response, as well as excretion of the metabolite 5-hydroxy-indoleacetic acid. , ,

Anxiety/Sleep terrorsAnimal data

Oral administration of an extract of G. simplicifolia seeds exerted an anxiolytic effect on rats subjected to dark-light and open field tests.

Clinical data

Studies in healthy volunteers found that oral administration of 5-HTP reduced the incidence of induced panic and associated symptoms when compared with placebo. , A gender difference in panic response was suggested in 1 small study. A study in children with sleep terrors reported a reduction of more than 50% in incidence with 5-HTP 2 mg/kg/day given at bedtime for 20 days. The effect of 5-HTP persisted in the majority of participants at the 6-month end point.

DepressionAnimal data

Studies in rodents have demonstrated the effect of 5-HTP on circulating serotonin levels and in sleep deprivation. Additionally, serotonin syndrome can be induced in rats given 5-HTP.

Clinical data

Approximately 30 clinical trials in depression have been conducted since the 1970s using 5-HTP. Following the occurrence of fatal eosinophilia associated with L-tryptophan and the advent of SSRIs, clinical studies were largely abandoned. , Of the published clinical studies, 11 were conducted in a double-blind manner. However, the trials used small numbers of participants, and the design of the trials, dosages, and duration were heterogeneous, making a meta-analysis impossible. Larger, more robust clinical trials are warranted to determine a place for 5-HTP in the management of depression. , A more recent exploratory study in healthy volunteers suggests a role for 5-HTP in the short-term setting while waiting for the onset of action of an SSRI.

Other effectsAggression

Studies in animals have found both inhibitory effects and heightened aggression with increased serotonin consequent to 5-HTP supplementation. Variables include the animal species used, length of treatment, and type of aggression. Clinical studies are lacking.

Appetite suppression

Studies in rats found decreased food intake and loss of weight with administration of G. simplicifolia extract. , A small (N = 20) clinical trial evaluated the effect of the extract on satiety among overweight women. Decreased appetite and a decrease in mean body mass index were demonstrated at 4 weeks. ,

Headache

Limited clinical studies were conducted in the 1980s. A more recent clinical trial found no effect of 5-HTP 300 mg/day on the number of tension-type (nonmigraine) headaches experienced during the 8-week study. However, in the 2-week period after treatment was stopped, a decrease in number of days with headache was observed. A difference over placebo was found for consumption of analgesics.

Menopause

A clinical trial evaluated the efficacy of 5-HTP 150 mg daily in the frequency of hot flashes, finding no difference over placebo.

Neurological diseases

Reviews of studies using 5-HTP in degenerative ataxia and pediatric neurotransmitter diseases suggest a potential role in reducing neurological symptoms; however, inconsistent findings have been reported. ,

Dosage

Studies in depression have used dosages varying from 20 to 3,250 mg daily; however, most commonly 200 to 300 mg/day has been used. , 5-HTP has a short half-life, and 3 to 4 divided doses are recommended to reduce the likelihood of nausea. ,

Studies have been conducted in children (range, 3 to 17 years of age). , , Because 100 mg given twice a day caused agitation in 20% of the participants (behaviorally at-risk children), the dosage was reduced to 100 mg/day.

In general, intravenous administration of 5-HTP at 20 mg gave an inadequate response, while at 40 mg caused severe nausea and vomiting, limiting its usefulness.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. 5-HTP has been shown to increase luteinizing hormone secretion in women, possibly via an increase in gonadotropin-releasing hormone.

Interactions

The potential for serotonin syndrome exists with concomitant use of SSRIs or MAOIs. Reports exist of serotonin syndrome consequent to L-tryptophan and fluoxetine combinations, but no reports to date can be attributed to 5-HTP. Studies have shown 5-HTP to augment the effect of citalopram and clomipramine. Carbidopa increases the bioavailability of 5-HTP.

Drug/Lab Test Interactions

5-HTP has been shown to increase the urinary levels of 5-hydroxyindoleacetic acid, a marker for carcinoid tumor, which may lead to misinterpretation of laboratory tests.

Adverse Reactions

Nausea and vomiting are the most common dose-related adverse events. Diarrhea, abdominal pain, mild headache, and sleepiness have also been reported. ,

Laboratory studies in rats have demonstrated a suppressive effect on sexual behavior with short-term doses of G. simplicifolia extract in both males and females; however, no effect was observed with dosing of up to 9 days' duration and clinical importance of this is unclear. ,

Toxicology

Research reveals little information regarding the toxicology of 5-HTP. A possible association with fatal eosinophilia-myalgia syndrome in the 1980s and 1990s has now been attributed to contaminated L-tryptophan. , , , HPLC identification of the implicated contaminant tryptophan-4,5-dione (referred to in publications as "Peak X") has also been disputed in a review of the safety of 5-HTP, but remains a requirement of the US Food and Drug Administration for all commercial 5-HTP products. Rats fed 5-HTP for a year showed no toxicological effects, and no reports of human toxicity have been documented since the mid-1990s.

Uses

Acacia gum has been used in pharmaceuticals as a demulcent. It is used topically for healing wounds and has been shown to inhibit the growth of periodontic bacteria and the early deposition of plaque.

Dosing

Gum acacia is usually used to modify the physical properties of foods. It was used in a clinical study of cholesterol reduction at a dose of 15 g per day.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Ingestion may raise serum cholesterol. Various forms of acacia gum can cause allergic reactions, including respiratory problems and skin lesions.

Toxicology

Acacia is essentially nontoxic when ingested.

Botany

The acacia tree ( A. senegal ; syn. with A. verek Guill et Perr.) is a thorny, scraggly tree that grows to heights of about 15 feet. It grows most prolifically in regions of Africa, in particular in the Republic of Sudan. During times of drought, the bark of the tree splits, exuding a sap that dries in small droplets or "tears." In the past, these hardened sap tears served as the major source of acacia gum, but today commercial acacia gum is derived by tapping trees periodically and collecting the resin semi-mechanically. At least three grades of acacia gum are available commercially and their quality is distinguished by the color and character in the collected tears. There is considerable variation in gum quality depending on whether it is obtained by natural flow secondary to extreme drought, obtained by tapping or induced by the boring of beetles at sites of branch injury. Gums derived from Combretum are readily available at low prices in East and West Africa and are often offered for sale as "gum arabic." Because there is no toxicologic data supporting the safety of these gums, they are not recognized as food additives by most countries. Similarly, trees of the genus Albizia are often confused with Acacia and should not be used as acacia substitutes.

History

Acacia gum has long been used in traditional medicine and in everyday applications. The Egyptians used the material as a glue and as a pain-reliever base. Arabic physicians treated a wide variety of ailments with the gum, resulting in its current name. Today, it is used widely in the pharmaceutical industry as a demulcent and in the cooking industry to give body and texture to processed food products. It also is used to stabilize emulsions. The fibers of the bark are used to make cordage.

Chemistry

Acacia gum is a brittle, odorless and generally tasteless material that contains a number of neutral sugars, acids, calcium and other electrolytes. The main component of the gum is arabin, the calcium salt of the polysaccharide arabic acid. The structure of the gum is complex and has not yet been fully explained. A comprehensive analysis, including NMR spectra for 35 samples of gum arabic, has been published to serve as the basis for international standardization of acacia gum. The gum is built upon a backbone of D-galactose units with side chains of D-glucuronic acid with L-rhamnose or L-arabinose terminal units. The molecular weight of the gum is large and estimates suggest the weight lies in the range of 200,000 to 600,000 daltons. It is very soluble in water, but does not dissolve in alcohol.

Uses and Pharmacology

Acacia gum has no significant systemic effects when ingested.

Cholesterol

Although related gums have been shown to be hypocholesterolemic when ingested, there is no evidence for this effect with acacia.

Animal data

Some studies suggest that ingestion of acacia gum may increase serum cholesterol levels in rats.

Clinical data

When administered to hypercholesterolemic patients for periods ranging from 4 to 12 weeks, acacia gum had no effect on the level of any plasma lipid evaluated. ,

Periodontal disease

Whole gum mixtures of acacia have been shown to inhibit the growth of periodontic bacteria, including Porphyromonas gingivalis and Prevotella intermedia in vitro when added to culture medium in concentrations ranging from 0.5% to 1%.

Animal data

Research reveals no animal data regarding the use of acacia gum for periodontal disease.

Clinical data

At a concentration of 0.5%, acacia whole gum mixture also inhibited bacterial protease enzymes, suggesting acacia may be useful in limiting the development of periodontal disease. In addition, chewing an acacia-based gum for 7 days has been shown to reduce mean gingival and plaque scores compared to a sugar-free gum; the total differences in these scores was significant ( P < 0.05) between groups suggesting that acacia gum primarily inhibits the early deposition of plaque.

Other uses

Acacia gum is a demulcent, and soothes irritated mucous membranes. Consequently, it is used widely in topical preparations to promote wound healing and as a component of cough and some gastrointestinal preparations.

In the past, the gum has been administered intravenously to counteract low blood pressure following surgery and to treat edema associated with nephrosis, but this administration caused renal and liver damage and allergic reactions, and its use was abandoned.

Dosage

Gum acacia is usually used to modify the physical properties of foods. It was used in a clinical study of cholesterol reduction at a dose of 15 g per day.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Allergic reactions to the gum and powdered forms of acacia have been reported and include respiratory problems and skin lesions. IV administration causes renal and liver damage.

Toxicology

Acacia is essentially nontoxic when ingested.

Acacia contains a peroxidase enzyme, which is typically destroyed by brief exposure to heat. If not inactivated, this enzyme forms colored complexes with certain amines and phenols and enhances the destruction of many pharmaceutical products including alkaloids and readily oxidizable compounds such as some vitamins. , Acacia gum reduces the antibacterial effectiveness of the preservative methyl-p-hydroxybenzoate against Pseudomonas aeruginosa , presumably by offering physical barrier protection to the microbial cells from the action of the preservative. A trypsin inhibitor also has been identified, but the clinical significance of the presence of this enzyme is not known.

Uses

Antioxidant and anti-inflammatory activity of acai has been documented. Folk medicinal uses include treatment of fever, pain, and flu. The fruit's dark green oil has been used as an antidiarrheal agent. However, there is a lack of clinical information to recommend acai for any use.

Contraindications

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

No data.

Toxicology

No data.

Botany

Acai, a member of the genus Euterpe , is indigenous to Central and South America and grows in the Amazon estuary as well as in swamps, upland regions, and floodplains. , , The acai palm is tall and slender, growing 15 to 30 m in height. The leaves are feather-like or pinnate in shape and grow up to 3 m in length. The plant is multistemmed and produces 3 to 4 bunches of round fruits 1 to 1.5 cm in diameter, with each bunch of fruit weighing 3 to 6 kg. The fruits appear in green clusters when immature and ripen to a dark purple color. Each acai fruit contains a seed that accounts for nearly 90% of its weight and diameter. The seeds are covered with a fibrous layer under which is a small edible layer. Although the fruits may be harvested throughout the year, the highest yields are obtained during the dry months of August through December versus the rainy months of January through July. ,

History

The fruit is of economic value; its juice is used to produce jelly, syrup, liquor, ice cream, energy drinks, and a variety of other beverages. Approximately 110,000 tons of fruit yield 100,000 tons of acai seeds commercially every year in the city of Belem, Brazil, alone. , , The frozen aqueous extract has been exported to numerous countries including the United States, Japan, the Netherlands, and Italy. The fruit also serves as a major food source for people indigenous to Brazil, Colombia, and Suriname. Folk medicinal uses include treatment of fever, pain, and flu. The fruit's dark green oil has been used as an antidiarrheal agent.

Heart of palm is a vegetable harvested from the inner core of various palm trees, including acai palm. It is considered a delicacy and is consumed pickled and in salad. The extraction of the heart of palm may lead to the death of the entire tree, which has economic implications; however, research has been undertaken to explore alternative solutions. , The scale of illegal palm heart harvesting is difficult to estimate.

There are numerous commercial acai products. Most claim antioxidant and antiaging properties. Topical formulations are promoted for inflammatory skin conditions, such as acne, and in hair restoration treatments. , Acai is used in cold and flu products and as a functional pigment for yogurt.

Chemistry

The primary medicinal part of the plant is the fruit or berry. Numerous studies have been completed on the nutritional composition and chemistry of the fruit. Acai fruit and berries contain lipids (49.4% and 33.1%), proteins (13.8% and 9.3%), ash (5.2% and 2.2%), and total dietary fiber (27.3% and 18%), respectively.

Another study on freeze-dried acai fruit identified 19 amino acids, making up 7.6% of total weight. Oleic acid (54%), palmitic acid (27%), and linoleic acid (12%) were the 3 dominant fatty acids. Nutrient analysis of 100 g of powder found 534 calories, 52 g carbohydrates, 8 g protein, 33 g total fat, and 44 g fiber. Vitamins A, B 1 , and C are present, as well as calcium and iron. Five sterols have also been isolated. The major phytochemicals include anthocyanins, proanthocyanidins, and other flavonoids, which are most likely associated with antioxidant activity. Cyandin 3-glucoside and cyanidin 3-rutinoside are the 2 predominant anthocyanins. , , Total analysis of all flavonoids in the fruit pulp and antioxidant capacity of the seed extract is documented.

Color and stability studies of acai in food, beverage, and nutraceutical products are also available. , Due to acai's deep pigmentation, it has been examined as an alternative oral contrast agent for imaging of the GI tract, GI motility, and evaluation of dyspepsia.

Uses and Pharmacology

Antioxidant and anti-inflammatory activity of acai has been studied.

Anticancer activityIn vitro

Acai fractions containing polyphenolic compounds reduced the proliferation of HL-60 leukemia cells through caspase-3 activation in a dose- and time-dependent manner. The mechanism of action is associated with polyphenolic phytochemicals activating caspase-3, leading to cell death or apoptosis.

Anti-inflammatory and antioxidant activityIn vitro

The total oxygen scavenging capacity of acai was high against peroxyl radicals, good for peroxynitrite, and mild for hydroxyl radicals when compared with other European fruit and vegetable juices. ,

Acai extracts inhibited lipopolysaccharide and interferon gamma-induced nitric oxide (NO) production in a macrophage cell line. Overproduction of NO may lead to activation of NO synthase, leading to the generation of cells mediating inflammatory processes. The mechanism of action is associated with inhibition of NO synthase expression and activity.

The antioxidant activities of the seeds are similar to those of the berries against peroxyl radicals. However, the seeds have a stronger antioxidant effect against peroxynitrite and hydroxyl radicals when compared with the berries.

Iron in acai fruits was not effective in improving hemoglobin concentrations in a rat study.

Prostate

An ethanol extract of acai palm fruit peel inhibited testosterone 5-alpha reductase. In patients with an enlarged prostate, dysuria was prevented by the administration of 2 tablets per day (80 mg of acai palm fruit peel extract powder per tablet) for 1 month.

Vasodilation

Acai induced an endothelium-dependent vasodilator effect in a rat mesenteric vascular bed. The mechanism of action appeared to be dependent on activation of NO-GMPc pathway and may involve endothelium-derived hyperpolarizing factor release.

Uses

Acerola provides natural vitamin C and other useful vitamins and minerals. It is used as an antioxidant as well as an antifungal agent. Other uses include as an astringent and for diarrhea, dysentery, hepatitis, and fever, although clinical trials are lacking.

Dosing

There is no clinical evidence to guide human dosage of acerola.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Large doses may produce GI distress. Prolonged, massive dosage may predispose to formation of renal calculi.

Toxicology

Vitamin C is readily excreted by the body and is not typically associated with toxicity.

Botany

Acerola (previously M. punicifolia L.) is native to the West Indies, but is also found in northern South America, Central America, Texas, and Florida. It grows as small shrubs or trees from 5 to 15 m in height. The branches are brittle and the leaves are glossy and dark to light green. The 5-petaled flowers range from pink to white in color. Acerola fruit is cherry-like, 3-lobed, bright red, and 1 to 2 cm in diameter, containing several small seeds. Mature fruits are soft, pleasant-tasting, and contain 80% juice. The fruits deteriorate rapidly once removed from the tree. , ,

History

Acerola is believed to originate from the Yucatan. Traditionally, the fruits have been used to treat dysentery, diarrhea, and liver disorders. Both species of Malpighia have been reported to be excellent sources of vitamin C. However, the fruit of M. emarginata is known more accurately as acerola and is one of the richest sources of vitamin C known.

Chemistry

Acerola contains from 1% to 4.5% vitamin C (1000 to 4500 mg/100 g) as ascorbic and dehydroascorbic acids in the edible portion of the fruit. This far exceeds the content of vitamin C in peeled oranges (about 0.05% or 50 mg/100 g). The content of vitamin C in acerola varies with ripeness (highest in green and lowest in fully ripened fruit), season, and climate.

Vitamin C analysis regarding acerola storage after picking finds freezing (-18°C) the fruits to be the best way to preserve vitamin C percentage, as compared with room temperature or refrigeration. Older reports evaluating ascorbic acid content in acerola are available. ,

Uses and Pharmacology

Vitamin supplementation

Acerola is used as a source of food and juice. Because of its high concentration of vitamin C, it also is sold as a natural health supplement.

Vitamin C is an essential coenzyme that is required for normal metabolic function. While many animals can synthesize vitamin C from glucose, humans must obtain the vitamin totally from dietary sources. Deficiencies of this water-soluble vitamin result in scurvy, a potentially fatal disease with multisystem involvement. Dietary supplements have traditionally provided adequate protection against the development of this disease.

However, controversy has focused on whether vitamin C derived from "natural" sources is more physiologic than that produced synthetically or semisynthetically (as ascorbic acid). To date, there is no clear evidence that naturally derived vitamin C is superior in its clinical effectiveness than synthetic ascorbic acid. A potential advantage to using acerola as a source of vitamin C is that one receives not only ascorbic acid, but also several other useful vitamins and minerals from the fruit. Whether this is superior to the use of a multiple vitamin preparation has not been determined.

Animal data

Research reveals no animal data regarding the use of acerola for vitamin supplementation.

Clinical data

Research reveals no clinical data regarding the use of acerola for vitamin supplementation.

AntioxidantMechanism of action

Vitamin C is known to strengthen the immune system, build collagen cells, support the respiratory system, and to be an effective antioxidant.

The antioxidative qualities of acerola make it an ideal ingredient in skin care products to fight cellular aging. In another report, acerola extract was shown to enhance the antioxidant activity of soy and alfalfa extracts, acting synergistically, which may be beneficial in coronary artery disease.

Animal data

Research reveals no animal data regarding the use of acerola as an antioxidant.

Clinical data

Research reveals no clinical data regarding the use of acerola as an antioxidant.

Antifungal

Acerola possesses antifungal properties. In one report, M. glabra was among the most active antifungal in 26 plants studied. The most susceptible fungi were E. floccosum and T. rubrum .

Animal data

Research reveals no animal data regarding the use of acerola as an antifungal agent.

Clinical data

Research reveals no clinical data regarding the use of acerola as an antifungal agent.

Other uses

Ethnobotanical uses of acerola include use as an astringent and for diarrhea, dysentery, hepatitis, and fever.

Dosage

There is no clinical evidence to guide human dosage of acerola.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

No specific adverse effects have been associated with the ingestion of acerola. However, the ingestion of large doses may induce GI side effects, including diarrhea. Prolonged use of massive doses of ascorbic acid may predispose to the development of renal calculi. ,

Toxicology

Because vitamin C is a water-soluble compound, it is readily excreted by the body, and it is not typically associated with toxicity.

Uses

The ackee is a major food in Jamaica. In South America, the fruit has been used to treat colds, fever, and diseases as varied as edema and epilepsy, although there are no clinical trials to support these uses.

Dosing

The ripe fruits are edible, however, the unripe fruits are toxic due to hypoglycins A and B.

Contraindications

The unripened ackee fruit is toxic, causing severe hypoglycemia often accompanied by convulsions and death.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.

Interactions

Hypoglycemia caused by ackee may be masked in patients on beta-blockers because these suppress epinephrine-mediated warning signs of imminent hypoglycemia; monitor patients with diabetes.

Adverse Reactions

No data.

Toxicology

Symptoms of ackee poisoning include cholestatic jaundice, vomiting, hypoglycemia, convulsions, coma, and potentially death. Six to 48 hours may elapse between ingestion of the unripened fruit and the onset of symptoms.

Botany

Ackee is the national fruit of Jamaica and is widely found throughout the West Indies and has been naturalized to parts of Central America, Florida, and Hawaii. This tall, leafy tree grows to approximately 12 meters and produces fruit 2 times/year, between January and March, and June and August. Its oval, compound leaves have 5 pair of leaflets, the longest of which is approximately 15 centimeters at the tip. The plant produces small, greenish-white flowers. The red fruit pods split open at maturity, exposing 3 shiny, black seeds embedded in a white, waxy aril.

History

The ackee tree was imported to Jamaica from West Africa in the late 1700s and is often grown as an ornamental. Although the unripened walnut-like seeds are toxic, the ripe fruits are used in traditional island cooking. The ackee is a major food in Jamaica and is noted for its high protein and fat content. Fresh ackee berries are available in season in markets and canned fruit is available throughout the year. Poisonings have long been associated with the use of the ackee, and published reports of Jamaican intoxications date back to 1904. In South America, the fruit is used to treat colds, fever, and diseases as varied as edema and epilepsy.

Chemistry

Hypoglycin A and hypoglycin B are potent hypoglycemic compounds. The most toxic is the cyclopropyl amino acid hypoglycin A and its metabolite methylenecyclopropylacetic acid, found in the aril and the seeds of the unripe ackee fruit. , , The unripe ackee fruit contains hypoglycin A at concentrations 100 times higher than those in ripe ackee fruit. , In addition, other hypoglycemic compounds, including hypoglycin B and other cyclopropanoid amino acids, are found in the seed. CNS active carboxycyclopropylglycines found in the unripened fruit are reported to be potent group II metabotrophic glutamate receptor agonists.

Uses and Pharmacology

The ackee is a major food in Jamaica. In South America, the fruit has been used to treat colds, fever, and diseases as varied as edema and epilepsy.

Animal data

Research reveals no animal data regarding the use of ackee for the treatment of colds, fevers, edema, or epilepsy.

Clinical data

Research reveals no clinical data regarding the use of ackee for the treatment of colds, fevers, edema, or epilepsy.

Dosage

The ripe fruits are edible, however, the unripe fruits are toxic due to hypoglycins A and B.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Avoid use.

Interactions

Hypoglycemia caused by ackee may be masked in patients on beta-blockers because these suppress epinephrine-mediated warning signs of imminent hypoglycemia; monitor patients with diabetes.

Adverse Reactions

Because ackee has no data supporting a medicinal use, all adverse reactions are addressed under Toxicology.

Toxicology

Hypoglycin A is a water-soluble liver toxin that induces hypoglycemia by inhibiting gluconeogenesis by limiting the activity of cofactor mimics (CoA and carnitine) that are required for the oxidation of long-chain fatty acids. Methylenecyclopropylacetyl-CoA also causes secondary inhibition of gluconeogenesis by inactivating several acyl-CoA dehydrogenases involved with the oxidation of fatty acids and several amino acids. The pink raphe (the portion of the seed that attaches to the ovary wall) and the aril in the immature plant are poisonous because of the presence of the hypoglycins. The arils become edible when the fruit ripens; hypoglycin A is efficiently removed from the edible arils when the ackee fruit is boiled in water for approximately 30 minutes. Hypoglycin A appears to be approximately twice as toxic as hypoglycin B. The powdered fruits are used in Africa as a fish poison.

More than 5000 people have died from ackee poisoning since 1886. , In the past, large-scale poisonings appeared to be limited to the island of Jamaica where they reached epidemic proportions during the winter months under the name of "Jamaican vomiting sickness." In Jamaica, 28 patients who had symptoms of ackee poisoning were identified during the period between January 1989 through July 1991. Six of these patients died. The most common symptoms were vomiting, coma, and seizures. Seven of the patients had confirmed hypoglycemia. Most of the cases occurred between January and March.

A case-control, retrospective study of health-service records and interviews with family members, village chiefs, and local healers in a rural area in west Africa identified 29 cases of fatal encephalopathy in preschool children (2 to 6 years of age) during January to May 1998. All children died within 48 hours of onset of symptoms. The clinical presentation was similar to that of Jamaican vomiting sickness and toxic hypoglycemic syndrome; most common symptoms included hypotonia, convulsions, and coma.

Eighty cases with symptoms consistent of ackee poisoning (ie, continuous vomiting, abdominal pains, loss of consciousness, convulsions within 24 hours) were recorded in 2 districts of Haiti's Northern Province between November 2000 and March 2001. Retrospective analysis confirmed 31 of the 80 cases were related to consumption of ackee. The mean age of the victims ranged from 6 months to 88 years, with a median of 7 and an average of 16. The case fatality rate was 52%.

Poisonings may be present in 1 of 2 distinct forms. In the first case, vomiting is followed by a remission period of 8 to 10 hours, followed by renewed vomiting, convulsions, and coma. The second type is characterized by convulsions and coma at the onset. Additional symptoms associated with chronic fruit ingestion include cholestatic jaundice, abdominal pain, and elevated liver function values. Diarrhea and fever are usually absent. Six to 48 hours may elapse between ingestion of the fruit and the onset of symptoms. Severe hypoglycemia develops and blood glucose levels as low as 3 mg/dL are observed in many cases.

Management of ackee intoxication consists of fluid therapy and the administration of glucose and electrolytes. Because patients with preexisting nutritional deficits and children may be more sensitive to the toxic effects of the fruit, vitamin and nutritional supplements should be administered. , ,

Uses

Aconite extracts have been used homeopathically in Europe and Asia (orally and externally), but rarely in the United States. Use is not recommended because of its toxicity.

Dosing

Extreme caution is required. Fresh aconite is extremely toxic, and safe dosage is dependent on processing. Many species are used medicinally in China only after processing. Traditional Western texts recommended 60 mg of the root per dose.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Interactions

None well documented.

Adverse Reactions

No data.

Toxicology

Aconitine is highly toxic. As little as 2 mg of pure aconite or 1 g of plant may cause death from paralysis of the respiratory center or cardiac muscle. Clinically important toxicity may develop following percutaneous absorption; even slight contact with the flowers can cause fingers to become numb.

Botany

Aconitine is an alkaloid derived from various species of Aconitum . At least 350 species exist throughout the world; about 170 species exist in China, and more than 100 species are found throughout the temperate zones of the United States and Canada. The plants are also found throughout many parts of Asia, Africa, and Europe. A. napellus is the most common species in Europe, and has been naturalized in the eastern United States; A. carmichaelii and A. kusnezoffii are the most common species used in traditional Chinese medicine. Aconitum species are erect perennial plants growing to a height of 0.6 to 1.5 m (2 to 6 feet). In general, they resemble delphiniums. The characteristic helmet-shaped blue or purple flowers grow in a raceme at the top of the stalk in summer or fall. Occasionally, the flowers may be white, pink, peach, or yellow. The seed pods contain numerous tiny seeds.

History

Various species of Aconitum have been used for centuries both as poisons and medicines. Some are still being used in traditional medicines of India, China, and Japan. The root is the most toxic, although all parts of the plant are considered to be toxic. The toxicity of the extracts follow the same order as the alkaloid content: roots, flowers, leaves, and stems.

Extracts of the Aconitum species have been used orally in traditional medicine to reduce fever associated with colds, pneumonia, laryngitis, croup, and asthma; and for their analgesic, anti-inflammatory, hypotensive, diuretic, diaphoretic (cause sweating), cardiac depressant (slow heart rate), and sedative properties. , In traditional Asian medicine, root extracts are typically mixed with other ingredients, such as licorice or ginger. Extracts also have been used as arrow poisons.

Historically, aconite was most commonly used in Western cultures as a tincture. It was applied topically as a counter irritant liniment for neuralgia, rheumatism, and sciatica.

In homeopathy, aconite is used to treat fear, anxiety, and restlessness; acute sudden fever; symptoms from exposure to dry, cold weather or very hot weather; tingling, coldness, and numbness; influenza or colds with congestion; and heavy, pulsating headaches.

Chemistry

Alkaloids account for up to 1.5% of the dry weight of Aconitum plant species. A wide variety of alkaloids have been isolated from the various species of aconite, including the major active alkaloid aconitine, as well as mesaconitine, hypaconitine, jesaconitine, napelline, sinomontanitines, lappaconitine, ranaconitine, and others. , , , , , Other alkaloids may be produced by processing (eg, pyro-type aconitine alkaloids by heat or benzylaconines or aconines by hydrolysis). Aconitine and its congeners are considerably more toxic than aconine and related alkaloids.

Uses and Pharmacology

Because aconite is highly toxic, its use is not recommended. Raw aconite products are extremely toxic; their alkaloids have a narrow therapeutic index and the alkaloid type and amount vary with species, place of harvest, and adequacy of processing. Processing may reduce alkaloid content and/or alter alkaloid composition, thus reducing potency; however, poisoning may still occur after the consumption of processed aconite root.

The following pharmacological effects of Aconitum alkaloid have been described: analgesic, anti-inflammatory, and anti-rheumatic activity , ; positive inotropic effects ; and regulation of neurological disorders. , However, only limited studies are available, and most were performed in China and Japan.

Animal data

In animal models, aconitine and related compounds have been shown to possess anti-inflammatory and analgesic properties. , , Studies using mechanical and thermal stimuli to cause pain in mice have shown that, at sub-analgesic doses, processed Aconitum root administered orally, both partially and dose-dependently inhibited the development of morphine tolerance in morphine-naive mice and reversed already developed morphine tolerance in morphine-tolerant mice when compared with placebo. , , ,

Human data

Results of a study using Japanese kampo preparations suggest that Aconiti tuber may increase nitric oxide production in humans, a possible mechanism for its purported effect on improving a peripheral feeling of coldness. Eleven and 13 patients, respectively, received kampo formulas including and excluding Aconiti tuber. The nitrite and nitrate levels were increased at 4 weeks in those taking Aconiti tuber formulas.

Clinical data

Research reveals no clinical data regarding the use of aconite for medical purposes.

Guanfu base A, a new alkaloid isolated from the root of A. coreanum Rapaics, has been found to be an effective antiarrhythmic agent in preclinical and clinical studies and is now undergoing phase 3 clinical trials in China.

Shenfu injection, a traditional Chinese therapy that contains red ginseng and aconite root, has provided a protective effect against ischemia and reperfusion injury during mitral valve replacement with cardiopulmonary bypass, and has also stimulated the immune system and reduce blood viscosity, improving postoperative recovery after abdominal surgery. However, the effect of the aconite component has not been determined.

Dosage

Extreme caution is required. Fresh aconite is extremely toxic, and safe dosage is dependent on processing. Many species are used medicinally in China after processing. Traditional Western texts recommended 60 mg of the root per dose. Pure aconite 2 mg or aconite plant 1 g may cause death.

Toxicology

Toxicity and death have resulted when the plant has been consumed accidentally, possibly mistaken for wild parsley, horseradish, or other herbs growing in the wild. , Very few cases of aconite poisoning have been reported in North America. Most reports have been related to the use of traditional Chinese remedies. A retrospective search of the Taiwan National Poison Center database between 1990 and 1999 revealed 17 cases of aconitine poisoning. Thirteen patients ingested aconite root for treatment of rheumatism or wounds. Two patients had volunteered to test the effects of aconite root in a drug study. Only 2 patients had accidentally ingested the root. The Toxicology Reference Laboratory in Hong Kong confirmed 10 cases of aconite poisoning between March 2004 and May 2006. In 4 cases, the aconite herb was not listed in written prescriptions.

Most incidents of aconite toxicity result from the wide variability in strength of home preparations in Asian countries. However, more lethal poisonings are being reported in Western countries where the use of herbal remedies is increasing. , A homicide attempt and a suicide with the plant have been reported.

Aconitine's toxicity is characterized by a burning or tingling sensation of the lips, tongue, mouth, and throat almost immediately following ingestion. Numbness of the throat and difficulty with speech may ensue. Salivation, nausea, vomiting, dizziness, and diarrhea may occur, as well as visual blurring or yellow-green color vision distortion, weakness, and incoordination. Paraesthesia may spread over the entire body. Toxicity mainly affects CNS, heart, and muscle tissues, primarily resulting in cardiovascular complications. , , , , Cardiac arrhythmias with unusual electrical characteristics have been observed following aconite poisoning. , Putrescine, a compound used experimentally as a molecular probe, has been shown to attenuate aconitine-induced arrhythmias. Death from aconitine may follow, secondary to cardiac arrhythmia, which can occur unpredictably within minutes or days. Several case reports describe poisonings with aconite or its constituents, resulting in ventricular tachycardia, other arrhythmias, and death. , , , , ,

A single dose of aconitine 0.6 mg/kg administered intraperitoneally to rabbits caused histopathologic damage to the myelin sheath of the visual pathway, spinal cord, and peripheral nerves. Similarly, aconitine has demonstrated arrhythmogenic and cardiotoxic effects on myocardium in anesthetized cats. Some experiments have used aconitine to artificially induce arrhythmias in laboratory animals to study the antiarrhythmic effects of other drugs. ,

A review has summarized the toxicological mechanisms of Aconitum alkaloids, which include the following: (1) binding to voltage-dependent sodium channels inducing a hyperpolarized state, resulting in permanent activation of the channel; (2) modulation of neurotransmitter release and receptors, particularly norepinephrine and acetylcholine; (3) promotion of lipid peroxidation of the cardiac system, possibly causing cardiac arrhythmias; and (4) induction of cellular apoptosis in the heart, liver, and other organs. Most of the cardiotoxic and neurotoxic effects can be explained by these mechanisms, including their effect on calcium imbalance.

General supportive measures, including fluids for dehydration, intravenous pressor agents (eg, dobutamine, dopamine) for hypotension, and resuscitative measures when indicated, form the basis of aconite toxicity management. , Gastric lavage or induction of emesis following the injection of atropine has been recommended. Control of cardiac dysrhythmias has been attempted with various antiarrhythmic agents (eg, lidocaine, amiodarone, flecainide, procainamide, mexiletine) ; however, no single antiarrhythmic drug has been uniformly effective. , Amiodarone and flecainide have been reasonable first-line choices. , , Several cases of successful treatment using percutaneous cardiopulmonary support and bypass in the first 24 hours have been reported. , , Charcoal hemoperfusion has also been used in patients with ventricular arrhythmias unresponsive to antiarrhythmic agents and supportive care, and may have played a critical role in patient survival. , Recovery time is dependent on amount of intoxication; mildly intoxicated patients may take 1 to 2 days to recover, whereas patients with cardiovascular complications may take 7 to 9 days to recover.

Evidence suggests that aconite may lose potency after undergoing certain manufacturing procedures; therefore, processed aconite may not have a toxicity profile similar to that of crude plant material.

Uses

Research on African mango shows beneficial effects for diabetes and obesity, as well as analgesic, antimicrobial, antioxidant, and GI activity. Ethnomedicinal treatments utilize the bark, kernels, leaves, or roots for a variety of ailments. Numerous studies exist on the potential industrial application of African mango in food, cosmetic, and pharmaceutical products.

Dosing

Clinical studies used dosage regimens of 150 mg of African mango seed extract 30 minutes before lunch and dinner or 1,050 mg 3 times daily 30 minutes before meals with a glass of warm water. Powders, liquids, and capsules are available from commercial manufacturers, with most common dosage regimens consisting of 150 mg of African mango twice a day with food.

Contraindications

Avoid use with a known allergy or hypersensitivity to any of the components of African mango.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Limited information is available regarding drug interactions. Because African mango delays stomach emptying, prescription medications should be coadministered with caution.

Adverse Reactions

Clinical studies enrolled a small number of patients, and mild side effects were documented. Adverse reactions included headache, dry mouth, GI complaints, sleep disturbance, and flu-like symptoms.

Toxicology

Acute toxicity studies documented no deaths within 24 hours or 7 days after administration of 1,600 mg/kg of African mango methanol extract to rats.

Botany

The African mango tree is found throughout the tropical forests of Africa and is also cultivated on farms in central and western Africa. The tree grows 10 to 40 m in height and has a flared base 3 m in height. The dark green foliage is dense and the leaves are elliptical. The yellow to white flowers occur in bundles or clusters from February to March, and the almost spherical fruit appear during the rainy season from July to September. The tree reaches maturity and begins flowering at 10 to 15 years of age, while flowering and fruiting times vary according to geographic location. The timber and wood of the tree are fine grained, hard, and durable. The ripe fruit is green while the edible mesocarp is soft, juicy, and bright orange. The mesocarp has a turpentine flavor and may taste sweet to slightly bitter. The seeds or kernels of the tree are classified as oilseeds. , , ,

History

Ethnomedicinal treatments utilize the bark, kernels, leaves, or roots for a variety of ailments. The bark is mixed with palm oil for treating diarrhea and for reducing the breast-feeding period. The shavings of the stem bark are consumed by mouth to treat hernias, yellow fever, and dysentery, and to reduce the effects of poison in French Equatorial Africa. The antibiotic properties of the bark help heal scabby skin, and the boiled bark relieves tooth pain. The Mende tribe in Sierra Leone grinds the bark into a paste with water and applies the product to the skin for pain relief. , In certain parts of Africa, the bark extract is ingested to produce an analgesic effect. The powdered kernels act as an astringent and are also applied to burns. The stems of the tree have been used as chewing sticks to help clean teeth.

African bush mango juice produces a quality wine at 8% alcohol content after 28 days of fermentation that in 1 study was comparable in color, flavor, sweetness, and acceptability to a German reference wine. , Additionally, the fresh bark has been used to alter the taste of palm wine.

The kernels of African mango are classified as oilseeds. The seeds are ground into a paste, also known as dika bread, which is valued for its food-thickening properties. The resulting product is used in soups, stews, or sauces. The fat extracted from the kernel is similar to margarine or cooking oil. Flour may also be produced from the kernels. , ,

Numerous studies exist on the potential industrial application of African mango in food, cosmetic, and pharmaceutical products. , , , , , , Agroforestry initiatives on phenotypic variation, amino acid profile, soil conditions, , and economic potential , of the plant species document additional commercial interest. The oil from the kernel may act as a binder in food or pharmaceutical products or as an industrial gum.

The pulp is used for making jam, jelly, and juice and is consumed as a dessert throughout western and central Africa. The leaves are used as food for livestock by farmers. The wood is used for making walking sticks and supports for thatched roofs.

Chemistry

Several studies have assessed the chemical properties of the kernels or seeds and pulp in African mango.

The seeds are a good source of nutrients, containing vitamins and minerals such as calcium, magnesium, potassium, sodium, phosphorus, and iron. , The pulp is also an excellent source of calcium (262 mg per 100 g) and vitamin C (66.7 mg per 100 mL).

Dika fat may serve a role in pharmaceutical drug-release systems. Dika fat out-performed magnesium stearate, stearic acid, and hydrogenated vegetable oil when tested in tablet equipment and imparted no adverse effect on the creation and integrity of hydrochlorothiazide tablets. Microencapsulation of aspirin with dika fat offered better protection against hydrolysis when compared with bee and carnauba wax. , At 5% and 10% weight/weight wax concentrations, dika wax and paraffin wax were comparable in ability to delay drug release from microcapsules. Dika fat has also been evaluated as a film coating for drug release in polymeric systems. Suppositories containing dika fat blends satisfied pharmaceutical requirements of drug release and stability.

Studies document that mucilage extracted from African mango seeds performed better than acacia and tragacanth in emulsion and suspension formulations. Dika nut mucilage may improve tablet strength and drug-release properties in tablet formulations.

Uses and Pharmacology

Research on African mango revealed beneficial effects on diabetes and obesity as well as antimicrobial, antioxidant, and GI activity.

DiabetesAnimal data

Dikanut fiber and cellulose were fed to diabetic rats over 4 weeks. The dikanut fiber supplement was more effective than cellulose at altering digestive and membrane-bound enzymes of the intestine and hepatic glycolytic enzymes, leading to reduced absorption of glucose. A similar study in streptozotocin-induced diabetic rats fed dikanut fiber resulted in reduced glucose, cholesterol, and triglyceride levels in plasma. Dikanut fiber supplementation also affected liver phospholipid distributions that may alter transport of lipids in the liver.

Although the study is limited, dikanut supplementation in diabetic patients over 4 weeks lowered blood glucose levels and normalized erythrocyte membrane ATPase activity. The ratio among the enzymes studied in diabetic patients was comparable to that of nondiabetic patients. A very similar study documents reduced plasma lipids in diabetic patients due to decreased low-density lipoprotein (LDL) plus very low-density lipoprotein (VLDL)-cholesterol and triglycerides levels. ATPase activity normalized and high-density lipoprotein (HDL) cholesterol was increased.

Obesity

Several potential mechanisms against obesity with African mango supplementation include:

Rats were fed a normal diet and 1 mL of African mango oil or water over 4 weeks. Abdominal fat was lower, plasma HDL cholesterol and triglyceride levels were higher, and LDL:HDL and total cholesterol:HDL ratios were lower in rats administered the oil. Blood glucose levels were also lower in rats administered the oil.

In a murine adipocyte model for adipose cell biology research, an African mango seed extract inhibited adipogenesis in adipocytes. The mechanism appears to be associated with (1) downregulated expression of adipogenic transcription factors or PPAR-gamma and adipocyte-specific proteins, such as leptin, and (2) upregulated expression of adiponectin. Adiponectin has antiatherogenic, anti-inflammatory, and antidiabetic activity.

A 1-month, randomized, double-blind, placebo-controlled, crossover study examined the effects of African mango seed extract in 40 obese patients. Patients were administered 3 capsules containing 350 mg of African mango seed extract (active formulation) or oat bran (placebo) 3 times daily 30 minutes before meals with a glass of warm water. Patients were on a normocaloric diet and were evaluated every week, as well as instructed to keep a record of food consumed. At the end of the study, patients treated with the seed extract had reduced body weight, waist and hip circumference, and metabolic parameters (eg, total cholesterol, LDL cholesterol, triglycerides), and increased HDL cholesterol. Patients treated with the extract also reported reduced systolic blood pressure. Another 10-week clinical study treating patients with a formulation of 2 plant materials, African mango and Cissus quadrangularis , resulted in reductions in body weight and improved metabolic parameters.

Other pharmacologic activityAnalgesic

In a mouse study, the analgesic activity of a water extract from African mango stem bark was comparable with the narcotic analgesic morphine, while the ethanol extract was comparable with the nonnarcotic analgesic methimazole sodium.

Antioxidant

One study documents antioxidant activity in African mango seeds.

Antimicrobial

African mango leaf and root extracts have documented inhibitory activity against several bacteria and fungi. , Potential mechanisms of action include membrane disruption by terpenoids and inactivation of microbial adhesion, enzymes, and cell envelope transport proteins by ellagic acid-like compounds.

Gastrointestinal

A methanol extract of African mango exhibited dose-dependent inhibition of indomethacin-induced gastric ulceration in mice. The antiulcer activity of several doses of the extract was comparable to that of cimetidine (50 mg/kg), and the extract also reduced gastric acid secretion and increased mucous secretion. Another animal study in mice administered African mango aqueous leaf extract reported decreased GI motility and GI protection against castor oil-induced diarrhea.

Dosage

Clinical studies used dosage regimens of 150 mg of African mango seed extract 30 minutes before lunch and dinner or 1,050 mg 3 times daily 30 minutes before meals with a glass of warm water. Powders, liquids, and capsules are available from commercial manufacturers, with most common dosage regimens consisting of 150 mg of African mango twice a day with food.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Limited information is available on drug interactions. Theoretically, African mango may enhance the side effects of medications used in diabetes and high cholesterol. Additive side effects may also be seen in patients treated with medications for obesity. Because African mango delays stomach emptying, prescription medications should be coadministered with caution.

Adverse Reactions

Avoid use with a known allergy or hypersensitivity to any of the components of African mango. Clinical studies enrolled a small number of patients, and mild side effects were documented. Adverse reactions included headache, dry mouth, GI complaints, sleep disturbance, and flu-like symptoms. , ,

Toxicology

Acute toxicity studies document no deaths within 24 hours or 7 days after administration of 1,600 mg/kg of African mango methanol extract in rats. One report detected fungi and aflatoxins in bush mango seeds sold in eastern Nigeria, which are unacceptable for human consumption.

Uses

The plant species has been examined for its activity against soil phytopathagens and as a mosquito repellant to prevent malaria and dengue fever. It has also been evaluated for its anti-inflammatory and chemotherapeutic activity and for use in diabetes.

Interactions

Adverse Reactions

Toxicology

None well documented. The constituent of O. canum , estragole, is carcinogenic.

Botany

The Lamiaceae family contains approximately 220 genera and nearly 4,000 species worldwide. , Numerous members of the family contain biologically active essential oils. O. canum is a semiperennial plant species found in Africa and Asia, but not native to North America. The plant grows 30 to 40 cm high and branches out from its base. It has angled stems and oval pubescent leaves. Its long flower spikes are pale to intense pink. The mature calyx is about 4 mm in diameter.

History

The plant is used medicinally in Africa to treat conjunctivitis, malaria, and headache. It also has been used to manage diabetes mellitus in Ghana and as an analgesic and rubefacient in other parts of Africa. Ethnopharmacology studies document its use in treating dysuria in Iran. The essential oils of the plant species have been used mainly as an antipyretic and for treating respiratory diseases on the eastern coast of Africa. The aerial plant parts or the leaves and flowers have been used with other spices for culinary purposes.

The essential leaf and flower oils have been used as flavoring in foods, chewing gums, sweets, teas, soft drinks, energy drinks, and milk products. The oils are also used in cosmetics, shampoos, soaps, shower gels, body lotions, and toothpastes.

Chemistry

O. canum essential oils from various origins occur as several physiological forms or chemotypes. , , , Most chemotypes have 2 major flavonoids, the most common being nevadensin and salvigenin. , Depending on geographical location, other examples include species with methyl cinnamate-rich oils from Central Africa, Comoro Island, India, São Tom , Aruba, and Nigeria. A citral type from East Africa and India, as well as a linalool-type from Rwanda, India, and Israel are documented. An eugenol type has additionally been described from samples in the United States and Nigeria. A camphor-type from India, Somali, and Zimbabwe has been described. Further documentation is available on the chemotypes. , , , ,

The seeds of O. americanum contain a high content of mucilage and have been studied as a disintegrant in tablet formulations.

Uses and Pharmacology

Anti-inflammatory, chemotherapeutic, and blood glucose-lowering activity is documented in the scientific literature. However, most research examines the plant's use against vector-borne diseases and as an insect repellent in agricultural soils.

Anti-inflammatory activity

Anti-inflammatory activity may be associated with the essential oils and linolenic acid content, which can block both the cyclooxygenase and lipoxygenase pathways of arachidonate metabolism. ,

The plant has been examined for its activity against soil phytopathogens and as a mosquito repellant to prevent malaria and dengue fever. Ethnobotanical studies document selective fungitoxicity of the essential oils against soil phytopathogens. The oils were not phytotoxic. In general, the plant is used in various parts of Africa to protect agricultural crops from insect damage. , , ,

When O. americanum potted plants were placed inside experimental huts, the entry of malaria vector mosquitoes decreased by nearly 40% compared with the use of a nonfragrant native grass. Ethnobotanical surveys also document that O. americanum is one of the most commonly used repellent plants in various villages and communities in Africa. , Malaria vector mosquitoes were repelled for up to 8 hours when the oils of O. americanum were combined with turmeric, citronella grass, and 5% vanillin.

The essential oils of O. americanum (LC 50 67 ppm) were also effective against the major vector of dengue fever, Aedes aegypti L., in a study completed in Brazil.

Uses

Agrimony is used as a tea and gargle for sore throat, and externally as a mild antiseptic and astringent.

Dosing

There is no published clinical evidence for a safe or effective dose; however, the German Komission E recommended a daily dose of 3 g of the herb for internal use. Agrimony also is used as a poultice from a 10% decoction of the herb.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Agrimony reportedly can produce photodermatitis.

Toxicology

No data.

Botany

Agrimony is a perennial herb with small, star-shaped yellow flowers. The plant possesses a short rhizome and is supported by a firm, hairy stem. The basal leaves are arrayed in a rosette and they, as well as the alternate sessile stem leaves, are pinnate, serrate and glabrous. The flowers and fruit (achene) grow at the top of the stem in a long, terminal spike. Agrimony is common in grasslands throughout Europe. It is imported from Bulgaria, Hungary and the former Yugoslavia.

History

The name Agrimonia may have its origin in the Greek "agremone" which refers to plants which supposedly healed cataracts of the eye. The species name eupatoria relates to Mithradates Eupator, King of Pontus, who is credited with introducing many herbal remedies. Its ancient uses include treatment for catarrh (mucous membrane inflammation with discharge), bleeding, tuberculosis and skin diseases. In folk medicine, it has been reported, without verification, to be useful in gallbladder disorders. Numerous other reported uses include use as a dye, flavoring, gargle for performers and speakers, antitumor agent, astringent, cardiotonic, coagulant, diuretic, sedative, antiasthmatic and for corns or warts.

Chemistry

The aerial parts of the plant contain 4% to 10% condensed tannins, small amounts of ellagitannins and traces of gallotannins. , Also reported are some 20% polysaccharides. A triterpenoid, ursolic acid, has been isolated. Silicic acid, traces of essential oil, and the flavonoids luteolin and apigenin 7-O-β-D-glucosides are present. Organic acids, vitamin B 1 , vitamin K and ascorbic acid are also found. The fresh herb contains agrimoniolide, palmitic and stearic acids, ceryl alcohol and phytosterols. Seeds contain 35% oil which contains oleic, linoleic and linolenic acids. ,

Uses and Pharmacology

Astringent

Agrimony is used widely in Europe as a mild astringent (externally and internally), particularly against inflammation of the throat, gastroenteritis and intestinal catarrh. Studies of ethanolic extracts have antiviral properties.

Animal data

Research reveals no animal data regarding the use of agrimony as an astringent.

Clinical data

Research reveals no clinical data regarding the use of agrimony as an astringent.

Other uses

This plant is often included in phytomedicine mixtures for "liver and bile teas," again without true scientific verification. Agrimony extracts are often used in small amounts in prepared European cholagogues and stomach and bowel remedies (eg, Neo-Gallonorm -Dragees) and urological products (eg, Rhoival ). Agrimony is also a component of the British product Potter's Piletabs . , , ,

Dosage

There is no published clinical evidence for a safe or effective dose; however, the German Komission E recommended a daily dose of 3 g of the herb for internal use. Agrimony also is used as a poultice from a 10% decoction of the herb.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Agrimony has been reported to produce photodermatitis in man.

Toxicology

Research reveals little or no information regarding toxicology with the use of this product.

Uses

Most of the medical literature documents the use of AHCC (active hexose correlated compound) as an immunomodulatory agent and its efficacy in therapy for cancer and various infections; however, there is limited information to support the use of this product for any condition.

Dosing

AHCC is primarily available as a capsule. The manufacturer's dosing guidelines recommend two 500 mg capsules by mouth 3 times a day on an empty stomach or 2 capsules by mouth daily for general well-being. A dose of 3 g/day of AHCC in one study led to an increase in specific innate immunity in 4 weeks.

Contraindications

Avoid use if hypersensitive to any of the components of AHCC or to basidiomycete mushrooms.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

A phase I trial reported mild GI complaints, including nausea, diarrhea, and bloating. Some patients also reported headache, fatigue, and foot cramps with the liquid form of AHCC.

Toxicology

A phase I trial documents that AHCC 9 g/day for 14 days had minimal adverse effects and was well tolerated by most patients.

AHCC is an extract prepared from mycelia of several species of basidiomycete mushrooms, including shiitake or Lentinus edodes , after being cultured in a liquid medium. ,

History

AHCC was developed in 1987 at the University of Tokyo Faculty of Pharmaceutical Sciences along with other researchers as a natural product to be used for regulating high blood pressure. However, AHCC is now primarily known for its immune stimulant potential in protecting against viruses, cancers, and infections. ,

AHCC is being researched in the United States, China, Korea, Japan, and Thailand. AHCC has been used as a supplement for patients with cancer, AIDS, hepatitis C, diabetes, hypertension, and autoimmune diseases. There are anecdotal claims for its use in treating wounds, stomach ulcers, gum disease, fatigue syndrome, parasites, and multiple sclerosis. ,

Chemistry

AHCC contains polysaccharides, amino acids, lipids, and minerals. , , It is obtained by a patented process involving cultivation, enzymatic decomposition, sterilization, concentration, and freeze-drying. The enzyme-fermented compound is an extract of the mycelia of basidiomycetes mushrooms. Oligosaccharides account for nearly 74% of AHCC, and approximately 20% of these saccharides are partially acetylated alpha-1,4 glucans with a mean molecular weight of 5,000 daltons. , The biological activities of AHCC are associated with the acetylated forms of the low molecular weight oligosaccharides. , ,

Uses and Pharmacology

Most of the medical literature documents the use of AHCC as an immunomodulatory agent and its efficacy in cancer and various infections; however, there is limited information to support the use of this product for any condition.

Cancer

AHCC is thought to modulate tumor immune surveillance by regulating innate and adaptive immune system responses. The compound may act as a biological response modifier by enhancing natural killer cell activity, interleukin-12 and tumor immunity production, and spleen cell proliferation and cytokine production.

In vitro and animal data

An in vitro study documents how the combination of AHCC plus UFT (tegafur/uracil) enhanced natural killer cell activity in tumor-bearing rats, while UFT treatment alone depressed the natural killer cell activity. In addition, the combination enhanced nitric oxide production and cytotoxicity of peritoneal macrophages. These actions, along with AHCC, restored suppressed mRNA expression of interleukin-1 alpha and tumor necrosis factor (TNF)-alpha induced by the chemotherapy and helped reduce metastasis of rat mammary adenocarcinoma.

AHCC partially suppressed DNA fragmentation on thymus apoptosis induced by dexamethasone in rats. AHCC may act as an antioxidant to suppress thymic apoptosis or stimulate melatonin secretion that protects thymocytes. AHCC administration enhanced the serum interleukin-12 level in H-2b mice and is effective in genetically Th1 (or transcription factor T-bet)-dominant mice. Interleukin-12 is considered a critical cytokine for immune system responses in anticancer therapy.

AHCC may help protect against adverse reactions caused by anticancer drugs. The compound protected against alopecia in rats treated with cytosine arabinoside. Liver injury was significantly reduced in rats treated with mercaptopurine and methotrexate when given AHCC at a dose of 1g/kg simultaneously.

Cisplatin-induced antitumor activity was enhanced with AHCC treatment in mice. AHCC improved the suppression of bone marrow caused by cisplatin, and histopathological examination of the kidney revealed a renal protective effect with AHCC supplementation.

Clinical data

In patients with malignant tumors, AHCC may increase circulating levels of TNF, interferon gamma, and interleukin 1B. A 2-week study reported that 3 and 6 g/day of AHCC increased natural killer cell activity in 3 patients with different types of advanced cancer: rhabdomyosarcoma, multiple myeloma, and breast cancer. The binding capacity of natural killer cells to tumor cells was enhanced 2-fold in 17 cancer patients with different advanced malignancies treated with 3 g/day of AHCC by mouth for 2 to 6 months. A similar 2-week study also documented a decline of tumor-associated antigens in 8 of 11 patients treated with AHCC. The mechanism of action was associated with enhanced natural killer cell activity due to an increase of natural killer cell granularity and binding capacity to tumor cell targets. Compared with baseline, interleukin-12, interferon gamma, and natural killer cell activity all increased to normal levels in 38 patients with solid tumors after treatment with AHCC.

AHCC may improve the prognosis of postoperative advanced liver cancer in patients by reducing its recurrence and incidence of death due to the condition or liver cirrhosis. ,

Serologic response improved after treatment with AHCC in a 66-year-old patient with castration-resistant prostate cancer, which is an incurable condition with limited treatment options.

One study of 12 different cancer patients reported that AHCC could be used to help prevent bone marrow depression from chemotherapy.

InfectionIn vitro and animal data

Oral administration of AHCC to food-deprived mice infected with Klebsiella pneumonia promoted clearance of the bacteria and resulted in reduced bacterial load. AHCC also enhanced early immune response by increasing levels of proinflammatory cytokines (ie, interleukin-12, TNF-alpha, and interleukin-6) and chemokines (MCP-1) that promote clearance and reduction of a variety of pathogens. AHCC decreased mortality, increased time to death, and increased clearance of K. pneumonia infection in mice. , A similar study in mice discovered that AHCC helped to restore immunity after trauma, infection, and food deprivation.

AHCC increased survival, enhanced natural killer cell activity in the lung and spleen, and rapidly cleared the primary influenza infection or virus from the lungs of infected mice. The compound works in a dose-dependent manner against acute influenza infection.

AHCC may be useful as a prophylactic drug in managing patients with opportunistic infections. The survival period for mice with cyclophosphamide-induced leukopenia was prolonged after oral or intraperitoneal administration of AHCC at 1,000 or 50 mg/kg/day prior to Candida albicans infection. The kidneys of infected mice also had decreased viable counts of C. albicans . Oral administration of AHCC protected mice from a lethal Pseudomonas aeruginosa infection and intraperitoneal administration protected mice from methicillin-resistant Staphylococcus aureus , infection.

AHCC administered to aged mice with West Nile encephalitis attenuated viremia levels but did not increase mortality.

Clinical data

Although the details of the study are lacking, clinical trials in Bangkok reported that HIV patients treated with AHCC have increased or maintained T-cell counts.

AHCC at 3 g/day was evaluated for 12 months in 20 HIV-positive men. The results of the study document the following : enhanced natural killer cell activity during the first month, which peaked at the third month and remained consistent during the trial; marked increase in absolute CD4+ cell counts in 14 of 20 patients during the first month and that remained consistent; no change in percentage of the CD4+ cells; increased absolute CD8 cell counts in 12 of 20 patients; and no change in the CD4/CD8 ratio.

Excess nitric oxide production may be involved with liver injury. AHCC may decrease inducible nitric oxide synthase (or iNOS) by reducing mRNA stabilization, rather than inhibiting its synthesis. ,

Dosage

AHCC is primarily available as a capsule. The manufacturer's dosing guidelines suggest administering two 500 mg capsules by mouth 3 times a day on an empty stomach or 2 capsules by mouth daily for general well-being. A dose of 3 g/day of AHCC in one study led to an increase in specific innate immunity in 4 weeks.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

AHCC did not inhibit CYP450 activity in one study; however, AHCC is a substrate and inducer of CYP450 2D6. Based on this study, AHCC has the potential for drug-drug interactions involving agents metabolized via CYP450 2D6 (eg, doxorubicin, ondansetron). Adverse drug reactions may potentially occur in patients taking psychiatric medications from the following drug classes: tricyclic antidepressants, selective serotonin reuptake inhibitors, or antipsychotics. Also monitor patients taking pain medications (eg, tramadol) and blood pressure medications, including beta-blockers, for potential adverse reactions.

Adverse Reactions

Historically, the safety profile of AHCC has been well established. A phase I trial documented mild GI complaints, including nausea, diarrhea, and bloating. Some patients reported headache, fatigue, and foot cramps with the liquid form of AHCC.

Toxicology

Avoid use with patients who are hypersensitive to any of the components of AHCC or to basidiomycete mushrooms. A phase I trial reported that 9 g/day of AHCC over 14 days resulted in minimal adverse reactions and was well tolerated by most patients. The median lethal dose of AHCC was 8,490 mg/kg in male rats and 9,849 mg/kg in female rats. Intraperitoneally, the minimal lethal dose of AHCC was lower in the male than in female rats, at 7,430 mg/kg and 8,340 mg/kg, respectively.